rs781036625

Variant names:

• chr1-8325853-C-G
• rs781036625
• NM_001080397.3:c.526C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-8325853-C-G
• chr1-8325853-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM5 PP3

The NM_001080397.3(SLC45A1):​c.526C>G​(p.Arg176Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R176W) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC45A1 NM_001080397.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

Genes affected

SLC45A1 (HGNC:17939): (solute carrier family 45 member 1) This gene was isolated initially from a region on chromosome 1p that is frequently deleted in human neuroblastoma, although no causal relationship has since been demonstrated. The encoded protein belongs to the glycoside-pentoside-hexuronide cation symporter transporter family and may play a role in glucose uptake. [provided by RefSeq, Mar 2014]

SLC45A1 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with neuropsychiatric features

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-8325853-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 428599.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080397.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A1	NM_001080397.3	MANE Select	c.526C>G	p.Arg176Gly	missense	Exon 4 of 9	NP_001073866.3	Q9Y2W3
	SLC45A1	NM_001379614.1		c.526C>G	p.Arg176Gly	missense	Exon 4 of 9	NP_001366543.1
	SLC45A1	NM_001379615.1		c.433C>G	p.Arg145Gly	missense	Exon 3 of 8	NP_001366544.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A1	ENST00000471889.7	TSL:5 MANE Select	c.526C>G	p.Arg176Gly	missense	Exon 4 of 9	ENSP00000418096.3	Q9Y2W3
	SLC45A1	ENST00000289877.8	TSL:1	c.526C>G	p.Arg176Gly	missense	Exon 3 of 8	ENSP00000289877.8	Q9Y2W3
	SLC45A1	ENST00000876633.1		c.526C>G	p.Arg176Gly	missense	Exon 4 of 9	ENSP00000546692.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461554 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	0.099
Eigen_PC	Benign	-0.00037
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.36	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.57	D
PhyloP100		2.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.32	N
REVEL	Pathogenic	0.68
Sift	Benign	0.23	T
Sift4G	Uncertain	0.053	T
Vest4		0.74
MutPred		0.58		Loss of methylation at R176 (P = 0.0158)
MVP		0.93
MPC		0.99
ClinPred		0.77	D
GERP RS		0.15
Varity_R		0.14
gMVP		0.84
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs781036625; hg19: chr1-8385913;